1999 Fiscal Year Final Research Report Summary
Study in Pharmacological Protection for Platelet Dysfunction during the Use of Blood contacting Artificial Organs
| Project/Area Number |
11671314
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| Research Category |
Grant-in-Aid for Scientific Research (C).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Fukui Medical University, Department of Surgery II |
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Principal Investigator |
TANAKA Kuniyoshi Fukui Medical University, Department of Surgery II, Professor, 医学部, 教授 (70144251)
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| Co-Investigator(Kenkyū-buntansha) |
YADA Isao Mie University School of Medicine, Department of Thoracic Surgery Professor, 医学部, 教授 (80093152)
NISHIKAWA Masakatsu Mie University School of Medicine, Department of Internal Medicine II, Associate Professor, 医学部・附属病院, 講師 (30144257)
CHIBA Yukio Fukui Medical University, Department of Surgery II, Associate Professor, 医学部, 助教授 (30111959)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Platetel / GPIIb / IIIa / GP Ib / GPIIb / IIIa antagonists / FK633 / abciximab / prostaglandin E1 |
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| Research Abstract |
Tne effects of FK633(a peptide-mimetic GPIIb/IIIa antagonist), abciximab(Reopro ; Fab fragment of antibody), and prostaglandin E1(PGE1)on platelet number and function were evaluated in an in-vitro model circuit which was composed of PVC tube, reservoir and a roller pump. The circuits were filled with heparinized blood(3U/ml)from healthy volunteers. The blood was divided into several groups according to the antiaggregant treatment ; group F, group A, group P received FK633(100〜500nM), abciximab(2〜10μg/ml), PGE1(50〜100ng/ml), respectively.In group A(10μg/ml)and group F(500nM), the platelet counts were better preserved than non-treatment group(group N). Reduction of surface GPIb expression was significantly less in the antiaggregant treatment groups. The expression of the P-selectin was significantly lower in the groups with GPIIb/IIIa antagonists. During and after circulation, the expression of PAC-1(activated GPIIb/IIIa)was significantly lower in the groups with anti-platelet groups, especially in the group A.
In summary, the GPIIb/IIIa antagonists and PGE1 reduced platelet activation in an in-vitro model circuit. This study indicated that it was important to inhibit the interaction between GPIIb/IIIa and fibrinogen. Therefore, FK633 may be a potential candidate for platelet protection during CPB.Because it has a potent inhibition of platelet activation, and its half-time is short.
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